CAM studies should meet research standards

Expert notes challenges in this field 

While interest in complementary and alternative medicine (CAM) research increases in the United States, there remain some significant challenges to properly designing these studies, an expert states.

"I personally don’t subscribe to the view that because CAM studies are difficult to design that we can’t maintain the rigor expected of other products, including pharmaceutical products," says Patricia Hibberd, MD, PhD, professor of medicine at Tufts University School of Medicine and division of clinical research resource at Tufts New England Medical Center in Boston.

"We have got to understand those challenges and how to deal with them," she says.

Here are some of the challenges of designing a CAM research protocol:

1. What is the composition of the product under study? "First, in order to know what you’re studying and to understand what the effects of the product are, you’ve got to know what the product is and, for patient safety, what’s in there and what’s not," Hibberd explains.

"I don’t have a lot of patience for studies where someone says it will cost a lot to buy a standard product," she adds. "I think, ethically, we’re required to get something to meet standards."

Since many CAM products are not regulated as drugs or biologics and the manufacturers do not make health claims that are approved by the FDA, then they may include items in the product which are not listed on the label, Hibberd notes.

"So it ends up being challenging figuring out how to do some of these studies," she adds. "We need to step up to the plate and say, How do we know what’s in the product and what’s not, so we’re not putting patients at risk.’"

The challenge for the researcher is to take the dietary supplement or other CAM product and learn precisely what is in the supplement and in what exact proportions, Hibberd suggests.

"If we can’t do that then should we be studying it in that format, or should we be studying something else that does meet that standard?" she asks.

2. When should safety be a top consideration and when should a data safety monitoring board (DSMB) be used? Too often, there is a tendency for CAM researchers to have an attitude that people have used this CAM product for 100 years, so why should safety be a major concern? Hibberd asks.

However, this overlooks the importance of conducting CAM research as rigorously as any other type of clinical research, she adds.

For example, a researcher might decide to provide triple doses of vitamin C to subjects and perhaps thinks there is no reason to worry about safety because everyone uses vitamin C, Hibberd says.

"But we have to look to see if high doses of vitamin C have adverse consequences," she says. "I wouldn’t consider doing a research study unless I had that information, even if it is appropriate to hypothesize that a higher level of vitamin C would be appropriate."

One rule of thumb is that if a particular patient population might warrant the establishment of a DSMB in a pharmaceutical product trial, then a DSMB should be used for a CAM trial as well, Hibberd notes.

"We need the same approaches to determine whether or not adverse events have occurred — as in a clinical trial, and we need the same oversight with a DSMB," she says. "What ever standards we’d expect for good clinical research outside of CAM, why should we consider CAM differently?"

Trial design and the double blind 

3. How does a clinical trial in CAM research use control groups and blind the study? "One of the areas that is very hard in CAM research is to blind subjects to what treatment group they’re in, particularly if you’re doing an intervention, for example," Hibberd says.

For instance, suppose an investigator wants to study the effects of tai chi and randomizes some subjects to engage in tai chi and others to not, she points out. "It’s obvious to folks who are getting it that they’re getting it."

"I understand it’s hard, but our job if we’re trying to understand CAM therapies is to come up with the strongest possible scientific design," Hibberd says. "And there are some great examples of how researchers have figured out how to do sham acupuncture for studies."

Likewise, perhaps a sham tai chi program could be created to provide a blinded quality to the study.

One methodological problem with this is that the tai chi master could be a charismatic person, and so the study might inadvertently study the effects of one group leader over another, Hibberd says. "The better conceived the design, the easier these protocols will be for the IRB to review."

4. What is the justification for the study? "If we have absolutely no idea at all how something might work then it really is difficult to justify why we’re doing a study," Hibberd notes.

For example, suppose an investigator is designing a study for a particular herb to see if it provides some therapeutic benefit when used to treat a particular condition, she says.

"If you asked for a rational basis for setting up the study for people with a particular illness, then you might not have a good reason for doing this particular study," Hibberd says.

"When trying to design scientifically valid research, and those are the ones the IRB really wants to be able to feel confident that the scientific rationale makes sense, then it really is hard when we don’t know much about how these products work," she says. "So you have to work backward and say a particular product is being used widely in this condition and, therefore, maybe we’re going to try to study whether it works."

Still, it’s difficult to answer skeptics who ask how a trial will determine how something is working and why it’s working, Hibberd notes.

"I personally think it would be helpful if some CAM researchers would stop jumping on I want to study a particular approach in this disease or that disease and, instead, say, I’ve got to understand how these things are working rather than come up with a rationale for doing research,’" she says.

From an IRB’s perspective, it’s better to know that there is a reason for doing a study, Hibberd notes. "Why waste people’s time?" she says. "A lot of these therapies are not likely to be risky, but some could be."